PRIME HFrEF: Novel Exercise for Older Patients With Heart Failure With Reduced Ejection Fraction

NCT ID: NCT05609097

Last Updated: 2025-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

92 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-14

Study Completion Date

2028-06-30

Brief Summary

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This study is trying to find out whether performing a hybrid aerobic-resistance exercise training program (titled PRIME: Peripheral Remodeling via Intermittent Muscular Exercise) results in better health outcomes than the traditional exercise training program (called COMBO) that is used in individuals with heart failure with reduced ejection fraction (HFrEF). Participants will be randomized (like the flip of a coin) to either PRIME (investigational) or the traditional exercise program (standard of care).

Detailed Description

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This study is a two-arm, prospective randomized clinical trial with participants randomized, in a 1:1 ratio to 4 weeks of either standard progressive whole-body aerobic plus resistance training (COMBO) or PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO assigned to all participants (Phase 2). The objective of this study is to determine whether PRIME exercise training can outperform traditional (COMBO) exercise training to improve outcomes in HFrEF patients. The study aims to test 92 HFrEF patients (46 randomized to PRIME and 46 to COMBO training) over a 5-year period. Data will be collected at each visit and patients will return for a 6-month follow up from the date of the final visit.

Conditions

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Heart Failure With Reduced Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective randomized open-label blinded endpoint (PROBE) parallel-group design. Participants will be randomized to PRIME or COMBO training for an initial four weeks (Phase 1). Following this, all participants will complete an additional eight weeks of COMBO training (Phase 2). Participants will be randomized in a 1:1 ratio by an independent statistician James Patrie (permuted block randomization with block size of 4, stratified by gender), with treatment allocation revealed after baseline exercise testing. Outcomes will be assessed at baseline, four weeks and eight weeks and 36 weeks (exploratory aim 5) by a blinded assessor (UVA SoM Exercise Core Laboratory).
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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PRIME + COMBO

PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO training.

Group Type EXPERIMENTAL

PRIME

Intervention Type OTHER

PRIME is a a 'hybrid' aerobic-resistance (cardio and weights) program designed to target all major muscle groups and address the muscle limitations responsible for reduced fitness in the elderly. This occurs by minimizing the central limitations to more traditional exercise by delivering an ideal exercise stimulus to muscles in a way in which the heart is not a limiting factor. Each exercise involves contractions of specific isolated muscle groups with a moderate load, defined as 40%-50% of their maximal voluntary capacity.

COMBO

Intervention Type OTHER

COMBO training includes both aerobic ("cardio") and resistance ("weightlifting") exercises. The aerobic component will be done on the stationary bicycle at 10-15 min duration at a target exercise intensity of 40-50% of VO2peak. This will feel like an intensity that is fairly light to somewhat hard, progressing gradually according to tolerance up to 20 mins. Intensity will be adjusted so that the difficulty remains in the target zone. The resistance component involves eight exercises, two sets of 10 repetitions, initially prescribed at 50-60% 1 repetition max. Subject will lift about half of their predicted maximal strength, 10 times, on 2 separate occasions with a rest between. Thereafter, the difficulty will be increased by approximately 10% when difficulty drops below the target range.

COMBO only

4 weeks of standard progressive whole-body aerobic plus resistance training (COMBO) followed by 8 weeks continued COMBO training.

Group Type OTHER

COMBO

Intervention Type OTHER

COMBO training includes both aerobic ("cardio") and resistance ("weightlifting") exercises. The aerobic component will be done on the stationary bicycle at 10-15 min duration at a target exercise intensity of 40-50% of VO2peak. This will feel like an intensity that is fairly light to somewhat hard, progressing gradually according to tolerance up to 20 mins. Intensity will be adjusted so that the difficulty remains in the target zone. The resistance component involves eight exercises, two sets of 10 repetitions, initially prescribed at 50-60% 1 repetition max. Subject will lift about half of their predicted maximal strength, 10 times, on 2 separate occasions with a rest between. Thereafter, the difficulty will be increased by approximately 10% when difficulty drops below the target range.

Interventions

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PRIME

PRIME is a a 'hybrid' aerobic-resistance (cardio and weights) program designed to target all major muscle groups and address the muscle limitations responsible for reduced fitness in the elderly. This occurs by minimizing the central limitations to more traditional exercise by delivering an ideal exercise stimulus to muscles in a way in which the heart is not a limiting factor. Each exercise involves contractions of specific isolated muscle groups with a moderate load, defined as 40%-50% of their maximal voluntary capacity.

Intervention Type OTHER

COMBO

COMBO training includes both aerobic ("cardio") and resistance ("weightlifting") exercises. The aerobic component will be done on the stationary bicycle at 10-15 min duration at a target exercise intensity of 40-50% of VO2peak. This will feel like an intensity that is fairly light to somewhat hard, progressing gradually according to tolerance up to 20 mins. Intensity will be adjusted so that the difficulty remains in the target zone. The resistance component involves eight exercises, two sets of 10 repetitions, initially prescribed at 50-60% 1 repetition max. Subject will lift about half of their predicted maximal strength, 10 times, on 2 separate occasions with a rest between. Thereafter, the difficulty will be increased by approximately 10% when difficulty drops below the target range.

Intervention Type OTHER

Other Intervention Names

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Exercise Exercise

Eligibility Criteria

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Inclusion Criteria

* Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
* Subjects may be of either sex with age \> 65 years.
* Subjects must be diagnosed with HFrEF as per established echocardiographic criteria (New York Heart Association Class II-III) with an ejection fraction \<45%.
* Cardiologist approve after thorough chart review and physical examination
* Hemoglobin of at least 10.0 g/dL

Exclusion Criteria

* Progressive worsening of exercise tolerance or dyspnea at rest or on exertion over previous 3-5 days
* Significant ischemia at low exercise intensities (\<2 METS or \~50 W)
* Uncontrolled diabetes (HbA1c \>10%)
* Acute systemic illness of fever
* Recent embolism (in the 6 weeks)
* Deep Vein Thrombophlebitis
* Active pericarditis or myocarditis
* Severe aortic stenosis (aortic valve area \<1.0 cm2)
* Regurgitant valvular heart disease requiring surgery
* Myocardial infarction within previous 3 weeks
* New onset atrial fibrillation (in the last 4 weeks)
* Resting Heart Rate \>120bpm
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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Jason Allen

principle investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jason Allen, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

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University of Virginia, Department of Kinesiology

Charlottesville, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ben Stephenson

Role: CONTACT

434-243-8677

Facility Contacts

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Ben Stephenson

Role: primary

434-243-8677

References

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Allen JD, Vanbruggen MD, Johannsen NM, Robbins JL, Credeur DP, Pieper CF, Sloane R, Earnest CP, Church TS, Ravussin E, Kraus WE, Welsch MA. PRIME: A Novel Low-Mass, High-Repetition Approach to Improve Function in Older Adults. Med Sci Sports Exerc. 2018 May;50(5):1005-1014. doi: 10.1249/MSS.0000000000001518.

Reference Type BACKGROUND
PMID: 29232316 (View on PubMed)

Shoemaker MJ, Curtis AB, Vangsnes E, Dickinson MG. Triangulating Clinically Meaningful Change in the Six-minute Walk Test in Individuals with Chronic Heart Failure: A Systematic Review. Cardiopulm Phys Ther J. 2012 Sep;23(3):5-15.

Reference Type BACKGROUND
PMID: 22993497 (View on PubMed)

Allen JD, Robbins JL, Vanbruggen MD, Credeur DP, Johannsen NM, Earnest CP, Pieper CF, Johnson JL, Church TS, Ravussin E, Kraus WE, Welsch MA. Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial". Contemp Clin Trials. 2013 Sep;36(1):266-75. doi: 10.1016/j.cct.2013.07.007. Epub 2013 Jul 27.

Reference Type BACKGROUND
PMID: 23900005 (View on PubMed)

Rickli H, Kiowski W, Brehm M, Weilenmann D, Schalcher C, Bernheim A, Oechslin E, Brunner-La Rocca HP. Combining low-intensity and maximal exercise test results improves prognostic prediction in chronic heart failure. J Am Coll Cardiol. 2003 Jul 2;42(1):116-22. doi: 10.1016/s0735-1097(03)00502-3.

Reference Type BACKGROUND
PMID: 12849670 (View on PubMed)

Angadi SS, Jarrett CL, Sherif M, Gaesser GA, Mookadam F. The effect of exercise training on biventricular myocardial strain in heart failure with preserved ejection fraction. ESC Heart Fail. 2017 Aug;4(3):356-359. doi: 10.1002/ehf2.12149. Epub 2017 Mar 16.

Reference Type BACKGROUND
PMID: 28772048 (View on PubMed)

Angadi SS, Mookadam F, Lee CD, Tucker WJ, Haykowsky MJ, Gaesser GA. High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study. J Appl Physiol (1985). 2015 Sep 15;119(6):753-8. doi: 10.1152/japplphysiol.00518.2014. Epub 2014 Sep 4.

Reference Type BACKGROUND
PMID: 25190739 (View on PubMed)

Other Identifiers

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1R01AG075556-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSR220112

Identifier Type: -

Identifier Source: org_study_id

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